Type 1 innate lymphoid cell aggravation of atherosclerosis is mediated through TLR4.

ILC populations elaborate a similar cytokine expression pattern with helper T cell subsets Th1, Th2 and Th17. Recent studies indicate that CD25+ILC2 could alleviate atherosclerosis by altering lipid metabolism, whereas the depletion of CD90-expressing ILCs had no influence on atherosclerosis. Thus, these findings raise the question of whether ILC1 cells react on atherosclerosis. Hence, our group attempted to explore the role of ILC1 cells in atherosclerosis. We found that ILC1 cells have a high Th1-like gene expression of T-bet and IFN-γ, which is distinct from ILC2, ILC3 or conventional NK (cNK) cells. Moreover, atherosclerotic lesions were greatly reduced in ApoE-/-Rag1-/- mice treated with anti-NK1.1 mAbs for depleting ILC1 cells (ILC1+cNK cells), compared to ApoE-/-Rag1-/- mice treated with anti-IL-15R mAbs for depleting cNK cells, and these effects could be fully rescued through the adoptive transfer of ILC1 cells sorted from the spleen of ApoE-/-TLR4+/+ mice into ApoE-/-Rag1-/- mice treated with anti-NK1.1 mAbs. However, the adoptive transfer of ILC1 cells sorted from the spleen of ApoE-/-TLR4-/- mice into ApoE-/-Rag1-/- mice treated with anti-NK1.1 mAbs blocked the progression of atherosclerosis, indicating that the pro-atherosclerotic role of ILC1 cells is dependent on TLR4. Furthermore, oxLDL-induced increase in IFN-γ expression from ApoE-/- ILC1 cells was correlated with the decrease in BACH2 expression. Taken together, ILC1 cells exist in atherosclerosis and aggravate atherosclerosis via increasing pro-inflammatory cytokine expression in a TLR4/BACH2-dependent manner.